This proposal is based on the applicant's recent denonstration that mice gradually lose cutaneous delayed hypersensitivity (DH) to several antigens and that specific DH is restored by administration of lymphoid tissue extracts from mice with active DH to the same or related antigens (24). Unexpressed, restorable DH has been designated cryptic delayed hypersensitivity (CDH). Specific research objectives are intended to further characterize CDH. 1) It is proposed to examine different modes of producing CDH, e.g., treatment with antigen concentrations which are too small to elicit skin-test positive DH, and exposure to antigens during periods of interferon-induced immune hyporeactivity and energy. 2) Studies are planned to delineate further those factors which restore specific cutaneous reactivity in mice with CDH. Preliminary observations that skin-test reactivity is restored during primary immunization to unrelated antigens will be pursued. Characterization of the immune responses which restore DH, and the host determinants controlling restoration also will be examined. 3) Several aspects of the mechanism(s) which operate in the establishment, maintenance and expression of CDH will be studied. Evaluation of immune cell regulatory function in mice with CDH will be emphasized. Immuno-regulatory activity will be examined in vivo by the adoptive transfer of lymphoid cells to and from mice with CDH. Antigen-induced cytotoxicity and tritiated thymidine incorporation by lymphocytes will be examined for use as in vitro CDH assays.